Helicobacter Pylori (H.P.) was classified as a Class I carcinogen by the World Health Organization in 1994. It is a Gram-negative bacterium that inhabits the surface of epithelial cells and is covered by mucus on the surface of the gastric mucosa. More than 50% of the world's population has Helicobacter Pylori infection in the upper gastrointestinal tract with up to 70% of infected people in developing countries, and 20% to 30% in developed countries. In acute infections, 20% of patients develop ulcers, and 1% of infected person may even develop gastric cancer or mucosa-associated lymphoma. In 2005, the Nobel Prize in Physiology or Medicine was awarded to two Australian scientists, Warren and Mashall, for their important role in discovering the effect of H. Pylori on digestive tract diseases and gastric cancer. The most common method for treating H. pylori is “triple therapy”, which uses a proton pump inhibitor and two antibiotics to remove H. pylori. However, patients are prone to relapse after administration, and often have adverse reactions such as nausea, diarrhea, and pseudomembranous colitis. Along with the frequent use of antibiotics, antibiotic-resistant strains of H. pylori have been continuously discovered, which has led to a gradual decrease in the efficiency of antibiotic treatment of H. pylori. Therefore, the development of H. pylori vaccine has always been a hot spot for scientists.
There are no vaccines on the market that prevent H. pylori infection or treat H. pylori currently. As a new target molecule for vaccine development, carbohydrate vaccines attract more and more attention by scientists. The polysaccharide structure on the surface of bacteria often plays an important role in the pathogenicity of bacteria and immune recognition in human body. Therefore, chemical synthesis of H. pylori surface oligosaccharides is of great significance to the development of H. pylori vaccine.
The oligosaccharide on the surface of H. pylori cells is Lipopolysaccharide (LPS). This LPS consists of O-antigen, core structure, and lipid A. There are a total of 6 serotypes for H. pylori, O1-O6, and the difference between them is mainly the difference in the O-antigen sugar moiety. The core structure of LPS for different serotypes of H. pylori is relatively conservative, so it is a good choice to chemically synthesize its core structure for use as a carbohydrate vaccine for the prevention and treatment of H. pylori infection. The core structure of H. pylori includes the inner core and the outer core. The latter is more likely to be exposed to the environment, and plays a very important role in the in vivo immune response caused by H. pylori infection.
The core structure of H. pylori lipopolysaccharide currently studied is mainly extracted from inactivated bacteria by biological methods. The defect is that the amount of product obtained by one extraction is usually small, the molecular structures obtained from extraction are not uniform, and the experimental repeatability is poor. Therefore, we selected the outer core octasaccharide of H. pylori as our target molecules for the chemical total synthesis. Through chemical synthesis, we can obtain a large number of target molecules with uniform and defined structures.